PURPOSE: Sixty percent of newly diagnosed patients with acute myeloid leukemia (ND-AML) receiving frontline therapy attain a complete response (CR), yet 30%-40% of patients relapse. Relapsed or refractory AML (R/R-AML) remains a particularly adverse population necessitating improved therapeutic options. This phase Ib/II study evaluated the safety and efficacy of fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin combined with the B-cell lymphoma-2 inhibitor venetoclax in ND-AML and R/R-AML. MATERIALS AND METHODS: The phase IB portion (PIB) enrolled patients with R/R-AML using a 3 + 3 dose escalation and de-escalation algorithm for identification of maximum tolerated dose and dose-limiting toxicities. The phase II portion enrolled patients into two arms to evaluate response and time-to-event end points: phase IIA (PIIA): ND-AML and phase IIB (PIIB): R/R-AML. RESULTS: Sixty-eight patients have enrolled to date (PIB, 16; PIIA, 29; PIIB, 23). Median age was 46 years (range, 20-73). Grade 3 and 4 adverse events occurring in ≥ 10% of patients included febrile neutropenia (50%), bacteremia (35%), pneumonia (28%), and sepsis (12%). The overall response rate for PIB, PIIA, and PIIB was 75%, 97%, and 70% with 75%, 90%, and 61%, respectively, achieving a composite CR. Measurable residual disease-negative composite CR was attained in 96% of ND-AML and 69% of R/R-AML patients. After a median follow-up of 12 months, median overall survival (OS) for both PII cohorts was not reached. Fifty-six percent of patients proceeded to allogeneic hematopoietic stem-cell transplantation (ND-AML, 69%; R/R-AML, 46%). In R/R-AML, allogeneic hematopoietic stem-cell transplantation resulted in a significant improvement in OS (median OS, NR; 1-year OS, 87%). One-year survival post-HSCT was 94% in ND-AML and 78% in R/R-AML. CONCLUSION: Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin + venetoclax represents an effective intensive treatment regimen in ND-AML and R/R-AML patients, associated with deep remissions and a high rate of transition to successful transplantation.
PURPOSE: Sixty percent of newly diagnosed patients with acute myeloid leukemia (ND-AML) receiving frontline therapy attain a complete response (CR), yet 30%-40% of patients relapse. Relapsed or refractory AML (R/R-AML) remains a particularly adverse population necessitating improved therapeutic options. This phase Ib/II study evaluated the safety and efficacy of fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin combined with the B-cell lymphoma-2 inhibitor venetoclax in ND-AML and R/R-AML. MATERIALS AND METHODS: The phase IB portion (PIB) enrolled patients with R/R-AML using a 3 + 3 dose escalation and de-escalation algorithm for identification of maximum tolerated dose and dose-limiting toxicities. The phase II portion enrolled patients into two arms to evaluate response and time-to-event end points: phase IIA (PIIA): ND-AML and phase IIB (PIIB): R/R-AML. RESULTS: Sixty-eight patients have enrolled to date (PIB, 16; PIIA, 29; PIIB, 23). Median age was 46 years (range, 20-73). Grade 3 and 4 adverse events occurring in ≥ 10% of patients included febrile neutropenia (50%), bacteremia (35%), pneumonia (28%), and sepsis (12%). The overall response rate for PIB, PIIA, and PIIB was 75%, 97%, and 70% with 75%, 90%, and 61%, respectively, achieving a composite CR. Measurable residual disease-negative composite CR was attained in 96% of ND-AML and 69% of R/R-AML patients. After a median follow-up of 12 months, median overall survival (OS) for both PII cohorts was not reached. Fifty-six percent of patients proceeded to allogeneic hematopoietic stem-cell transplantation (ND-AML, 69%; R/R-AML, 46%). In R/R-AML, allogeneic hematopoietic stem-cell transplantation resulted in a significant improvement in OS (median OS, NR; 1-year OS, 87%). One-year survival post-HSCT was 94% in ND-AML and 78% in R/R-AML. CONCLUSION: Fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin + venetoclax represents an effective intensive treatment regimen in ND-AML and R/R-AML patients, associated with deep remissions and a high rate of transition to successful transplantation.
Authors: Hartmut Döhner; Elihu Estey; David Grimwade; Sergio Amadori; Frederick R Appelbaum; Thomas Büchner; Hervé Dombret; Benjamin L Ebert; Pierre Fenaux; Richard A Larson; Ross L Levine; Francesco Lo-Coco; Tomoki Naoe; Dietger Niederwieser; Gert J Ossenkoppele; Miguel Sanz; Jorge Sierra; Martin S Tallman; Hwei-Fang Tien; Andrew H Wei; Bob Löwenberg; Clara D Bloomfield Journal: Blood Date: 2016-11-28 Impact factor: 22.113
Authors: Curtis A Lachowiez; Sanam Loghavi; Tapan M Kadia; Naval Daver; Gautam Borthakur; Naveen Pemmaraju; Kiran Naqvi; Yesid Alvarado; Musa Yilmaz; Nicholas Short; Maro Ohanian; Sherry R Pierce; Keyur P Patel; Wei Qiao; Jing Ning; Koji Sasaki; Koichi Takahashi; Elias Jabbour; Michael Andreeff; Farhad Ravandi; Hagop M Kantarjian; Marina Konopleva; Courtney D DiNardo Journal: Blood Adv Date: 2020-04-14
Authors: J E Parker; A Pagliuca; A Mijovic; J O Cullis; B Czepulkowski; S M Rassam; I R Samaratunga; R Grace; P A Gover; G J Mufti Journal: Br J Haematol Date: 1997-12 Impact factor: 6.998
Authors: Bruce D Cheson; John M Bennett; Kenneth J Kopecky; Thomas Büchner; Cheryl L Willman; Elihu H Estey; Charles A Schiffer; Hartmut Doehner; Martin S Tallman; T Andrew Lister; Francesco Lo-Coco; Roel Willemze; Andrea Biondi; Wolfgang Hiddemann; Richard A Larson; Bob Löwenberg; Miguel A Sanz; David R Head; Ryuzo Ohno; Clara D Bloomfield; Francesco LoCocco Journal: J Clin Oncol Date: 2003-12-15 Impact factor: 44.544
Authors: Roland B Walter; Sarah A Buckley; John M Pagel; Brent L Wood; Barry E Storer; Brenda M Sandmaier; Min Fang; Boglarka Gyurkocza; Colleen Delaney; Jerald P Radich; Elihu H Estey; Frederick R Appelbaum Journal: Blood Date: 2013-07-11 Impact factor: 22.113
Authors: Chong Chyn Chua; Andrew W Roberts; John Reynolds; Chun Yew Fong; Stephen B Ting; Jessica M Salmon; Sarah MacRaild; Adam Ivey; Ing Soo Tiong; Shaun Fleming; Fiona C Brown; Sun Loo; Ian J Majewski; Stefan K Bohlander; Andrew H Wei Journal: J Clin Oncol Date: 2020-07-20 Impact factor: 50.717
Authors: Andrew H Wei; Stephen A Strickland; Jing-Zhou Hou; Walter Fiedler; Tara L Lin; Roland B Walter; Anoop Enjeti; Ing Soo Tiong; Michael Savona; Sangmin Lee; Brenda Chyla; Relja Popovic; Ahmed Hamed Salem; Suresh Agarwal; Tu Xu; Kaffa M Fakouhi; Rod Humerickhouse; Wan-Jen Hong; John Hayslip; Gail J Roboz Journal: J Clin Oncol Date: 2019-03-20 Impact factor: 44.544
Authors: Hagop M Kantarjian; Nitin Jain; Guillermo Garcia-Manero; Mary Alma Welch; Farhad Ravandi; William G Wierda; Elias J Jabbour Journal: Cancer Date: 2021-10-06 Impact factor: 6.860
Authors: Hagop Kantarjian; Nicholas J Short; Courtney DiNardo; Eytan M Stein; Naval Daver; Alexander E Perl; Eunice S Wang; Andrew Wei; Martin Tallman Journal: Lancet Haematol Date: 2021-10-20 Impact factor: 18.959
Authors: Jacqueline S Garcia; Haesook T Kim; H Moses Murdock; Corey S Cutler; Jennifer Brock; Mahasweta Gooptu; Vincent T Ho; John Koreth; Sarah Nikiforow; Rizwan Romee; Roman Shapiro; Fiona Loschi; Jeremy Ryan; Geoffrey Fell; Hannah Q Karp; Fabienne Lucas; Annette S Kim; Danielle Potter; Thelma Mashaka; Richard M Stone; Daniel J DeAngelo; Anthony Letai; R Coleman Lindsley; Robert J Soiffer; Joseph H Antin Journal: Blood Adv Date: 2021-12-28
Authors: Pau Montesinos; B Douglas Smith; Joshua F Zeidner; Tara L Lin; Carlos E Vigil; Gil Fine; M Yair Levy; Aziz Nazha; Jordi Esteve; Daniel J Lee; Karen Yee; Andrew Dalovisio; Eunice S Wang; Juan M Bergua Burgues; Jeffrey Schriber; Mark R Litzow; Olga Frankfurt; Teresa Bernal Del Castillo; Vijaya Raj Bhatt; Bhavana Bhatnagar; Priyanka Mehta; Richard Dillon; Maria Vidriales Vicente; Stephen Anthony; David Bearss Journal: Blood Cancer J Date: 2021-10-30 Impact factor: 11.037